The composition of the cerebrospinal fluid and brain are closely regulated by mechanisms in the central nervous system that tend to accumulate substances necessary for brain functioning as vitamins and to exclude unnecessary substances as certain drugs. This exclusion of such drugs as penicillin and gentamicin from the cerebrospinal fluid and brain makes the therapy of certain infectious diseases of the nervous system difficult. The objects of the proposed studies are: (1) to gain further information about the development and function of these transport mechanisms in healthy animals as well as those with experimentally induced diseases as meningitis, brain abscess, and uremia; (2) to gain insight into the biochemical mechanisms underlying these transport processes; and (3) to manipulate or work around these transport mechanisms to the diseases animals; (and ultimately the patients') advantage. Particular attention will be devoted to transport processes and mechanisms located in the choroid plexus and to methods that will optimize antibiotic concentrations in the cerebrospinal fluid and surrounding tissues. To achieve these goals, the transport of radiolabeled drugs and vitamins into and out of the cerebrospinal fluid, choroid plexus and brain, in vivo, and into the choroid plexus and brain slices, in vitro, in both normal animals as well as those with experimental diseases will be documented under various conditions.